tbuckley/cabot-search huggingface dataset:
DS21: How can skin surgery outcomes be improved for patients with implanted devices?
Journal: British Journal of Dermatology (2022)

MIS, the majority of which underwent 2-mm margin excisions.For LM on the head and neck area, there was an 18% recurrence rate, with the majority of these cases occurring despite a 5-mm WLE.These results suggest that while closely related histologically, these conditions behave very differently clinically and a revision of national guidance on excision margins is required.
Extended Focal Ablation of Localized Prostate Cancer With High-Frequency Irreversible Electroporation
Authors: Haifeng Wang, Wei Xue, Weigang Yan, Lei Yin, Baijun Dong, Biming He, Yongwei Yu, Wentao Shi, Zhien Zhou, Hengzhi Lin, Yi Zhou, Yanqing Wang, Zhenkai Shi, Shancheng Ren, Xu Gao, Linhui Wang, Chuanliang Xu
Journal: JAMA Surgery (2022)

Focal therapy of prostate cancer must balance the oncologic outcome and functional outcome. High-frequency irreversible electroporation (H-FIRE) can destroy cancer cells while selectively preserving surrounding nerves and blood vessels, but no clinical trials have been conducted, to our knowledge.To evaluate the efficacy and safety of H-FIRE in the treatment of localized prostate cancer (PCa).This was a single-group, objective performance criteria, nonrandomized controlled trial. Recruitment began on May 2, 2018, and ended March 27, 2019. The follow-up duration was 6 months. This was a multicenter trial conducted at 4 tertiary teaching hospitals in China. Patients with low or intermediate risk of biochemical recurrence of localized and locally advanced PCa were eligible. Key inclusion criteria were serum prostate-specific antigen (PSA) level less than 20 ng/mL, clinical stage of T2c or less, and Gleason score of 7 or less. Data were analyzed from January 20 to February 20, 2021.H-FIRE ablation of all lesions identified with biopsy.The primary end point was 6-month clinically significant PCa (csPCa), which was defined as any biopsy core with Gleason score of greater than or equal to 7, or Gleason score of 6 plus maximum cancer core length of greater than 3 mm or an increase from the original cancer burden. Secondary outcomes were calculated in patients who actually received H-FIRE treatment.A total of 117 patients (median [IQR] age, 67 [62-73] years) were recruited from 4 centers, and 109 patients (27 [24.8%] low risk and 82 [75.2%] intermediate risk) actually received H-FIRE. Median (IQR) PSA level was 9.0 (6.0-12.7) ng/mL. Among the 100 patients who underwent biopsy at 6 months, the 6-month csPCa rate was 6.0% (95% CI, 2.2%-12.6%; P < .001; 1 in the treatment zone and 5 outside the treatment zone). Superiority criteria vs the historical control of 20% was achieved. PCa was detected in 14 patients, with a Gleason score of 7 in 2 patients and 6 in the remaining 12 patients. At 6 months, median (IQR) PSA level was 1.08 (0.4-3.2) ng/mL, median (IQR) International Prostate Symptom Score was 4.5 (2.0-9.5), and median (IQR) International Index of Erectile Function 5 score was 2.0 (0.5-12.5). Superiority vs the 20% historical control was also met in the subgroup analysis that only included the 57 patients with Gleason score of 7 at baseline (3.5% 6-month csPCa; 95% CI, 0.4%-12.1%).The rate of 6-month csPCa with H-FIRE ablation was lower than the historical control using other energy platforms.ClinicalTrials.gov Identifier: NCT03838432.
Nonsteroidal Topical Treatment for Plaque Psoriasis Is Approved
Authors: Howard D. Larkin
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Correction Notice: Antifungal Prophylaxis in Acute Myeloid Leukemia: New Drugs, New Challenges? Summary of the EHA Guideline on Antifungal Prophylaxis in Adult Patients With Acute Myeloid Leukemia Treated With Novel-targeted Therapies
Journal: HemaSphere (2022)

[This corrects the article DOI: 10.1097/HS9.0000000000000742.].
Errors in Abstract and Text
Journal: JAMA Pediatrics (2022)

Jan Łukasik, MD; Thomas Dierikx, MD; Isolde Besseling-van der Vaart, MSc; Tim de Meij, MD, PhD; Hania Szajewska, MD, PhD; Multispecies Probiotic in AAD Study Group; Sophie R. D. van der Schoor; Malika Chegary; Catharina (Karen) J.M. Koning
New Daily Persistent Headache—A Start With an Uncertain End
Authors: Amy A. Gelfand, Matthew S. Robbins, Christina L. Szperka
Journal: JAMA Neurology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Endoscopic ultrasound-guided choledochoduodenostomy with pyloric occlusion by proximal flange of electrocautery-enhanced lumen-apposing metal stent: solving a rare adverse event
Authors: Danilo Paduano, Francesco Auriemma, Federica Spatola, Laura Lamonaca, Alessandro Repici, Benedetto Mangiavillano
Journal: Endoscopy (2022)

An 80-year-old woman presented to our emergency room with jaundice, nausea, and vomiting. An abdominal tomography revealed intrahepatic biliary ducts and common bile duct (CBD) dilation because of an inhomogeneous hypoechoic mass of 2 × 1.5 cm in its distal part and an absence of distant metastases. After a multidisciplinary case discussion it was decided to perform an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) of the mass and drainage of the CBD.
Genomic and epigenomic <i>BRCA</i> alterations predict adaptive resistance and response to platinum-based therapy in patients with triple-negative breast and ovarian carcinomas
Authors: Francesca Menghi, Kalyan Banda, Pooja Kumar, Robert Straub, Lacey Dobrolecki, Isabel V. Rodriguez, Susan E. Yost, Harshpreet Chandok, Marc R. Radke, George Somlo, Yuan Yuan, Michael T. Lewis, Elizabeth M. Swisher, Edison T. Liu
Journal: Science Translational Medicine (2022)

Triple-negative breast cancer (TNBC) and ovarian carcinomas (OvCas) with BRCA1 promoter methylation (BRCA1meth) respond more poorly to alkylating agents compared to those bearing mutations in BRCA1 and BRCA2 (BRCAmut). This is a conundrum given the biologically equivalent homologous recombination deficiency (HRD) induced by these genetic and epigenetic BRCA perturbations. We dissected this problem through detailed genomic analyses of TNBC and OvCa cohorts and experimentation with patient-derived xenografts and genetically engineered cell lines. We found that despite identical downstream genomic mutational signatures associated with BRCA1meth and BRCAmut states, BRCA1meth uniformly associates with poor outcomes. Exposure of BRCA1meth TNBCs to platinum chemotherapy, either as clinical treatment of a patient or as experimental in vivo exposure of preclinical patient derived xenografts, resulted in allelic loss of BRCA1 methylation and increased BRCA1 expression and platinum resistance. These data suggest that, unlike BRCAmut cancers, where BRCA loss is a genetically "fixed" deficiency state, BRCA1meth cancers are highly adaptive to genotoxin exposure and, through reversal of promoter methylation, recover BRCA1 expression and become resistant to therapy. We further found a specific augmented immune transcriptional signal associated with enhanced response to platinum chemotherapy but only in patients with BRCA-proficient cancers. We showed how integrating both this cancer immune signature and the presence of BRCA mutations results in more accurate predictions of patient response when compared to either HRD status or BRCA status alone. This underscores the importance of defining BRCA heterogeneity in optimizing the predictive precision of assigning response probabilities in TNBC and OvCa.
P78: Secukinumab treatment results in sustained improvement in absolute Psoriasis Area and Severity Index and Dermatological Life Quality Index in biologic‐naïve and biologic‐experienced patients with moderate‐to‐severe plaque psoriasis: analysis of 12 months of follow‐up data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)
Journal: British Journal of Dermatology (2022)
Manjula Arora: would most “ordinary decent people” conclude that she had acted dishonestly?
Authors: Jay Ilangaratne
Journal: BMJ (2022)

Sharks are modern descendants of the earliest vertebrates possessing Ig superfamily receptor–based adaptive immunity. They respond to immunogen with Abs that, upon boosting, appear more rapidly and show affinity maturation. Specific Abs and immunological memory imply that Ab diversification and clonal selection exist in cartilaginous fish. Shark Ag receptors are generated through V(D)J recombination, and because it is a mechanism known to generate autoreactive receptors, this implies that shark lymphocytes undergo selection. In the mouse, the ∼2.8-Mb IgH and IgL loci require long-range, differential activation of component parts for V(D)J recombination, allelic exclusion, and receptor editing. These processes, including class switching, evolved with and appear inseparable from the complex locus organization. In contrast, shark Igs are encoded by 100–200 autonomously rearranging miniloci. This review describes how the shark primary Ab repertoire is generated in the absence of structural features considered essential in mammalian Ig gene assembly and expression.
Biological Misinterpretation of Transcriptional Signatures in Tumor Samples Can Unknowingly Undermine Mechanistic Understanding and Faithful Alignment with Preclinical Data
Authors: Natalie C. Fisher, Ryan M. Byrne, Holly Leslie, Colin Wood, Assya Legrini, Andrew J. Cameron, Baharak Ahmaderaghi, Shania M. Corry, Sudhir B. Malla, Raheleh Amirkhah, Aoife J. McCooey, Emily Rogan, Keara L. Redmond, Svetlana Sakhnevych, Enric Domingo, James Jackson, Maurice B. Loughrey, Simon Leedham, Tim Maughan, Mark Lawler, Owen J. Sansom, Felicity Lamrock, Viktor H. Koelzer, Nigel B. Jamieson, Philip D. Dunne
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Precise mechanism-based gene expression signatures (GES) have been developed in appropriate in vitro and in vivo model systems, to identify important cancer-related signaling processes. However, some GESs originally developed to represent specific disease processes, primarily with an epithelial cell focus, are being applied to heterogeneous tumor samples where the expression of the genes in the signature may no longer be epithelial-specific. Therefore, unknowingly, even small changes in tumor stroma percentage can directly influence GESs, undermining the intended mechanistic signaling. Experimental Design: Using colorectal cancer as an exemplar, we deployed numerous orthogonal profiling methodologies, including laser capture microdissection, flow cytometry, bulk and multiregional biopsy clinical samples, single-cell RNA sequencing and finally spatial transcriptomics, to perform a comprehensive assessment of the potential for the most widely used GESs to be influenced, or confounded, by stromal content in tumor tissue. To complement this work, we generated a freely-available resource, ConfoundR; https://confoundr.qub.ac.uk/, that enables users to test the extent of stromal influence on an unlimited number of the genes/signatures simultaneously across colorectal, breast, pancreatic, ovarian and prostate cancer datasets. Results: Findings presented here demonstrate the clear potential for misinterpretation of the meaning of GESs, due to widespread stromal influences, which in-turn can undermine faithful alignment between clinical samples and preclinical data/models, particularly cell lines and organoids, or tumor models not fully recapitulating the stromal and immune microenvironment. Conclusions: Efforts to faithfully align preclinical models of disease using phenotypically-designed GESs must ensure that the signatures themselves remain representative of the same biology when applied to clinical samples.
The (R)evolution of Social Media in Oncology: Engage, Enlighten, and Encourage
Authors: Gilberto Morgan, Neeraj Agarwal, Toni K. Choueiri, Don S. Dizon, Erika P. Hamilton, Merry Jennifer Markham, Mark Lewis, Tatiana M. Prowell, Hope S. Rugo, Vivek Subbiah, Howard L. West
Journal: Cancer Discovery (2022)

Social media (SoMe) platforms have the ability to strengthen the oncology community, leading to intellectual connections that with time develop into friendships. SoMe has immense potential in all areas of medicine, and SoMe in oncology is proof of this, raising awareness about clinical trials, promoting cancer prevention techniques, amplifying oncology information, enabling diverse viewpoints into conversations, as well as educating colleagues regardless of geography.
Type of Oral Anticoagulant and Adverse Clinical Outcomes in Patients Extending Anticoagulation Therapy Beyond 90 Days After Hospitalization for VTE
Authors: Renin Chang, Chih-Cheng Lai
Journal: JAMA (2022)

To the Editor We have several concerns about the recent study1 that demonstrated no significant difference in major bleeding with extended-duration direct oral anticoagulant (DOAC) therapy beyond 90 days after initial discharge for venous thromboembolism (VTE).
Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application
Authors: Fusheng Zhang, Haiyang Liu, Meiqi Duan, Guang Wang, Zhenghou Zhang, Yutian Wang, Yiping Qian, Zhi Yang, Xiaofeng Jiang
Journal: Journal of Hematology & Oncology (2022)

Abstract The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, and immunosuppression. One of the most common RNA modifications, N6-methyladenosine (m 6 A) methylation, is widely involved in the regulation of physiological and pathological processes, including tumor development. Compelling evidence indicates that m 6 A methylation regulates transcription and protein expression through shearing, export, translation, and processing, thereby participating in the dynamic evolution of TME. Specifically, m 6 A methylation-mediated adaptation to hypoxia, metabolic dysregulation, and phenotypic shift of immune cells synergistically promote the formation of an immunosuppressive TME that supports tumor proliferation and metastasis. In this review, we have focused on the involvement of m 6 A methylation in the dynamic evolution of tumor-adaptive TME and described the detailed mechanisms linking m 6 A methylation to change in tumor cell biological functions. In view of the collective data, we advocate treating TME as a complete ecosystem in which components crosstalk with each other to synergistically achieve tumor adaptive changes. Finally, we describe the potential utility of m 6 A methylation-targeted therapies and tumor immunotherapy in clinical applications and the challenges faced, with the aim of advancing m 6 A methylation research.
IFNα Potentiates Immune-Checkpoint Blockade by Rewiring Metabolic Cross-talk
Authors: Kung-Chi Kao, Alison Jaccard, Ping-Chih Ho
Journal: Cancer Discovery (2022)

Summary: In this issue, Hu and colleagues unveil that IFNα administration combined with anti–PD-1 therapy can potentiate murine and human CD8+ T-cell antitumor response in hepatocellular carcinoma, highlighting a novel therapeutic strategy for hepatocellular carcinoma. See related article by Hu et al., p. 1718 (6) .
A Cathepsin-Targeted Quenched Activity–Based Probe Facilitates Enhanced Detection of Human Tumors during Resection
Authors: Gregory T. Kennedy, David E. Holt, Feredun S. Azari, Elizabeth Bernstein, Bilal Nadeem, Ashley Chang, Neil T. Sullivan, Alix Segil, Charuhas Desphande, Eric Bensen, John T. Santini, John C. Kucharczuk, Edward J. Delikatny, Matthew Bogyo, A.J. Matthew Egan, Charles W. Bradley, Evgeniy Eruslanov, Jason D. Lickliter, Gavin Wright, Sunil Singhal
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Fluorescence-guided surgery using tumor-targeted contrast agents has been developed to improve the completeness of oncologic resections. Quenched activity–based probes that fluoresce after covalently binding to tumor-specific enzymes have been proposed to improve specificity, but none have been tested in humans. Here, we report the successful clinical translation of a cathepsin activity–based probe (VGT-309) for fluorescence-guided surgery. Experimental Design: We optimized the specificity, dosing, and timing of VGT-309 in preclinical models of lung cancer. To evaluate clinical feasibility, we conducted a canine study of VGT-309 during pulmonary tumor resection. We then conducted a randomized, double-blind, dose-escalation study in healthy human volunteers receiving VGT-309 to evaluate safety. Finally, we tested VGT-309 in humans undergoing lung cancer surgery. Results: In preclinical models, we found highly specific tumor cell labeling that was blocked by a broad spectrum cathepsin inhibitor. When evaluating VGT-309 for guidance during resection of canine tumors, we found that the probe selectively labeled tumors and demonstrated high tumor-to-background ratio (TBR; range: 2.15–3.71). In the Phase I human study, we found that VGT-309 was safe at all doses studied. In the ongoing Phase II trial, we report two cases in which VGT-309 localized visually occult, non-palpable tumors (TBRs = 2.83 and 7.18) in real time to illustrate its successful clinical translation and potential to improve surgical management. Conclusions: This first-in-human study demonstrates the safety and feasibility of VGT-309 to label human pulmonary tumors during resection. These results may be generalizable to other cancers due to cathepsin overexpression in many solid tumors.
The effect of vitamin D supplementation on risk of keratinocyte cancer: an exploratory analysis of the D-Health randomized controlled trial
Authors: Sitwat Ali, Hai Pham, Mary Waterhouse, Catherine Baxter, Briony Duarte Romero, Donald S.A. McLeod, Bruce K. Armstrong, Peter R. Ebeling, Dallas R. English, Gunter Hartel, Jolieke C. van der Pols, Alison J. Venn, Penelope M. Webb, David C. Whiteman, Rachel E. Neale
Journal: British Journal of Dermatology (2022)

Vitamin D may play a role in prevention of keratinocyte cancer (KC), but observational studies examining the association between serum 25-hydroxy vitamin D concentration and KC are largely uninformative because sun exposure causes both KC and vitamin D production. There is scant evidence from clinical trials of supplementary vitamin D.To examine the effect of vitamin D supplementation on the risk of developing KC.We used data from the D-Health Trial, a randomized placebo-controlled trial of vitamin D supplementation (60 000 international units monthly for 5 years) among Australians aged ≥60 years. KC outcomes were captured through linkage to a national administrative dataset for those who consented (N = 20 334; 95%). We used negative binomial regression to analyse the incidence of KC excisions and the incidence of actinic lesions treated using cryotherapy or serial curettage, and flexible parametric survival models for analysis of time to first KC excision.Randomization to vitamin D supplementation did not reduce the incidence of KC lesions treated by excision [incidence rate ratio (IRR) 1·04; 95% confidence interval (CI) 0·98-1·11], the incidence of actinic lesions treated using other methods (IRR 1·01; 95% CI 0·95-1·08) or time to first histologically confirmed KC excision (hazard ratio 1·02; 95% CI 0·97-1·08). However, in subgroup analysis vitamin D increased the incidence of KC excisions in adults aged ≥ 70 years (IRR 1·13, 95% CI 1·04-1·23; P-value for interaction = 0·01).Vitamin D supplementation did not reduce the incidence of KC or other actinic lesions. What is already known about this topic? Laboratory studies have suggested possible protective effects of vitamin D on skin cancer. Observational studies investigating the association between vitamin D and risk of keratinocyte cancer are largely uninformative as ultraviolet radiation both causes skin cancer and is the primary source of vitamin D. The evidence from randomized controlled trials of vitamin D is limited and inconclusive. What does this study add? This population-based, randomized controlled trial suggests that supplementing older adults with a high monthly dose of vitamin D for 5 years does not affect the incidence of keratinocyte cancer.